Research
Summary
|
Retina
Intracellular
Messenger Molecules.
Every cell in the body has a cadre of intracellular messenger molecules
that signal and regulate when some enzymes and small cellular enterprises
should decrease or increase their activity. >Like a town crier,
these internal messengers must physically "walk" through
the cell to regulate activity. Unlike the town crier, who can shout
louder when necessary, messenger molecules "speak" in
a single, |
Rods and Cones of the Retina |
even voice. Therefore in times of need,
thesignal for concerted action in the cell's township depends on unleashing
large groups of messengers. Because the cell must keep activity on
an even keel most of the time, there are strong regulatory mechanisms
to keep the number of messengers at reasonable levels. A principal
goal in my laboratory is to identify the town crier molecules within
cells of the retina, to determine what activities they can inhibit
or excite, and to determine how the number of these molecules is controlled
in normal times and in "emergencies."
We have identified both calcium ions and protons as molecules that
control activities within single cells. The importance of these "town
crier" functions performed by molecules, such as calcium, are
very important. For example, extended elevated calcium is one of the
principal means by which cells are killed. In the brain and retina,
there is no regeneration of nerve cells, so it becomes even more critical
to control calcium levels, not only for performing everyday activities
but for the life of the cell. In spite of this knowledge, relatively
little is known about how calcium enters nerve cells of the retina,
or how calcium is extruded. We are studying both of these mechanisms
in the retina.
There are two principal techniques by which cells pump calcium from
cells. One is a high-capacity exchanger that uses the stored energy
of each cell to pump calcium from the cell. The other calcium pump
is a low-capacity pump that switches on when needed, much as an automatic
sump pump works in a basement. Recent discovery of so called calcium-indicator
dyes now enables researchers to directly measure calcium in single
cells and thereby to get a peek at the regulatory mechanisms in cells.
Calcium Regulation.
One must approach the study of retinal cells by probing the activity
of single cells that can be isolated from the retina. We are studying
calcium regulation in individual rods and cones. We have discovered
that rods and cones use both types of pumps to control calcium in
the cells. The large-capacity pump regulates calcium that controls
how well the cells respond to light, and the more sensitive low-capacity
pump controls the calcium that regulates signaling to the next order
of neurons that eventually signal the brain.
Our long-term goal is to identify all processes that regulate calcium
in cells of the retina. One hope is that therapeutic manipulation
of these processes may help to preserve cellular function of retinal
neurons in disease states and during progressive degenerations that
occur in patients with retinitis pigmentosa and patients with macular
degeneration. |
| |
|
